Treatment of rats for 4 days with
alpha-methyldopa, 200 mg/kg/day i.p., increases steady state levels of
proopiomelanocortin (
POMC)
mRNA in the mediobasal hypothalamus, as measured by
DNA excess
solution hybridization. The increase is prevented by parallel treatment with
yohimbine, 2 mg/kg/day i.p., but not by
naltrexone, 2 mg/kg/day i.p. Treatment with the peripheral
vasodilator hydralazine, 2 mg/kg/day, does not affect
POMC mRNA levels. In situ hybridization histochemistry with a
cRNA probe for
POMC indicates that
POMC-containing cells are located within the confines of the arcuate nucleus both in control and in
alpha-methyldopa-treated rats, and confirms the increase in
POMC mRNA in the latter. Microinjection of 2 micrograms of
alpha-methylnorepinephrine unilaterally into the arcuate nucleus of
urethane-anesthetized rats causes
hypotension and
bradycardia, which can be inhibited by 200 ng of
yohimbine microinjected into the same site, or by 100 ng l-
naloxone microinjected into the ipsilateral nucleus tractus solitarii, but not into the arcuate nucleus. These findings are interpreted to indicate that activation of alpha 2-adrenergic receptors located on
POMC-containing neurons in the arcuate nucleus causes
beta-endorphin release and stimulation of
opiate receptors in the NTS, which results in
hypotension and
bradycardia, and that this mechanism contributes to the hypotensive action of
alpha-methyldopa.